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. 2017 Jul 31;7:6965. doi: 10.1038/s41598-017-06022-4

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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5-HT3R mediates tear secretion and lacrimal gland morphology. (A) Changes in tear secretion and (B) LG weight by continuous infusion of 5-HTR antagonists (n = 5 mice). Mice were infused with saline (vehicle) or each 5-HT3R antagonist for 7 days via an osmotic pump. Data show the changing ratio of each antagonist to saline with tear secretion (open column) and LG weight (solid column) at day 7 after infusion. Way-100635, ketanserin, ondansetron, and SB269970 were used as antagonists for 5-HT1aR, 5-HT2aR, 5-HT3R, and 5-HT7, respectively. (C) Effect of an agonist for 5-HT3R (SR57227A) on tear secretion under a condition of decreased blood 5-HT. SR57227A or vehicle (saline) was infused 1 day before changing to a Trp-free diet (n = 5 mice). (D) LG weight after SR57227A infusion (n = 10 LG). Histopathological changes in LG by infusion of (E) ondansetron or (F) SR57227A (scale bar is 10 µm). Changes in expression of LC3-II by infusion of (G) ondansetron or (H) SR57227A (n = 5 LG). Representative western blot image and quantitative analysis of the western blot (bar chart). (I) Effect of ondansetron on stimulated tear secretion by 5-HT. Ondansetron was simultaneous injected with 5-HT. Open circle, closed circle, and closed triangle indicate injection of vehicle, 5-HT, and 5-HT with ondansetron, respectively. (J) Stimulated tear secretion by SR57227A. Open circle and closed circle indicate injection of vehicle and SR5727A, respectively. Each drug was injected 2 days after changing to a Trp-free diet (I,J n = 5 mice). Data represent the 7 days after injection of a 5-HTR antagonist (B,E,G) and after changing to a Trp-free diet (D,F,H). Open and solid symbols show the infusion of vehicle and ondansetron or SR57227A, respectively (A–D,G,H). All data represent the mean ± SD. ***P < 0.001 versus saline (A,B), vehicle (C,D,G,H), or 0 min (I,J).